Abstract
BackgroundThe standard of care for colorectal peritoneal carcinomatosis is evolving from chemotherapy to cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with disease limited to the peritoneum. Peritoneal carcinomatosis from colorectal cancer treated with chemotherapy alone results in median survival of 5 to 13 months, whereas CRS with HIPEC for early peritoneal carcinomatosis from colorectal cancer resulted in median survival of 48-63 months and 5 year survival of 51%.Completeness of cytoreduction and limited disease are associated with longer survival, yet early peritoneal carcinomatosis is undetectable by conventional imaging. Exploratory laparotomy can successfully identify early disease, but this approach can only be justified in patients with high risk of peritoneal carcinomatosis. Historical data indicates that patients presenting with synchronous peritoneal carcinomatosis, ovarian metastases, perforated primary tumor, and emergency presentation with bleeding or obstructing lesions are at high risk of peritoneal carcinomatosis. Approximately 55% of these patient populations will develop peritoneal carcinomatosis. We hypothesize that performing a mandatory second look laparotomy with CRS and HIPEC for patients who are at high risk for developing peritoneal carcinomatosis from colorectal cancer will lead to improved survival as compared to patients who receive standard of care with routine surveillance.Methods/DesignThis study is a prospective randomized trial designed to answer the question whether mandatory second look surgery with CRS and HIPEC will prolong overall survival compared to the standard of care in patients who are at high risk for developing peritoneal carcinomatosis from colorectal cancer (CRC). Patients with CRC at high risk for developing peritoneal carcinomatosis who underwent curative surgery and subsequently received standard of care adjuvant chemotherapy will be evaluated. The patients who remain without evidence of disease by imaging, physical examination, and tumor markers for 12 months after the primary operation will be randomized to mandatory second look surgery or standard-of-care surveillance. At laparotomy, CRS and HIPEC will be performed with intraperitoneal oxaliplatin with concurrent systemic 5-fluorouracil and leucovorin. Up to 100 patients will be enrolled to allow for 35 evaluable patients in each arm; accrual is expected to last 5 years.Trial RegistrationClinicalTrials.gov ID: NCT01095523
Highlights
The standard of care for colorectal peritoneal carcinomatosis is evolving from chemotherapy to cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with disease limited to the peritoneum
Multiple reports of metastatic disease demonstrate an increased survival with current chemotherapeutic regimens [5,6,7,8,9,10], Elias et al reports the only series that follows patients with peritoneal carcinomatosis (PC) without systemic dissemination treated with current standard of care systemic chemotherapy regimens of FOLFOX (5-fluorouracil (5-FU), leucovorin, and oxaliplatin) and FOLFIRI (5fluorouracil (5-FU), leucovorin, and irinotecan)
This study revealed that high-risk patients with recurrent PC are often detected only at laparotomy despite appropriate surveillance and that the early detection of disease may result in complete CRS compared to CRS of symptomatic disease or disease detected by imaging
Summary
118 patients in a French registry showed a median overall survival of 5.2 months [4] Most of these patients received systemic 5-FU and leucovorin-based regimens. Verwaal et al [24] performed a RCT of CRS and HIPEC versus systemic chemotherapy alone which demonstrated a significant survival benefit with increase in median survival of 22 mo. 2-year survival of 44% versus 22%, respectively Even though this trial demonstrates a clear benefit, the systemic therapy with 5-FU and leucovorin is an outdated regimen compared to current treatment of FOLFOX or FOLFIRI. A multi-institutional registry [25] of 506 patients who underwent CRS and HIPEC for CRC with PC demonstrated a 1-, 3-, and 5year survival of 72%, 39%, and 19%, respectively with a median survival of 19 months. A prospective randomized trial has been designed to evaluate MSLS with CRS and HIPEC versus treatment of PC once disease is detected, during routine surveillance, by imaging or symptoms
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